In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence

In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence

JBUR 5161 No. of Pages 9 burns xxx (2017) xxx –xxx Available online at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locat...

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JBUR 5161 No. of Pages 9

burns xxx (2017) xxx –xxx

Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.elsevier.com/locate/burns

In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence Michal Brichacek a , Chenxi Ning c , Justin P. Gawaziuk b, Song Liu c,d, Sarvesh Logsetty a,b,e, * a

Department of Surgery, Section of Plastic and Reconstructive Surgery, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada b Manitoba Firefighters Burn Unit, Winnipeg,Manitoba, Canada c Department of Textile Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, Manitoba, Canada d Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Canada e Department of Surgery and Children’s Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

article info

abstract

Article history:

Purpose: There is a paucity of research on reducing dressing adherence. This is partly due to

Accepted 7 January 2017

lack of an in vitro model, recreating the clinical variability of wounds. Previously we

Available online xxx

described an in vitro gelatin model to evaluate adherence in a standardized manner. We present evaluation of strategies to reduce adherence in six dressings.

Keywords: Dressing Adherence Burns Gelatin In vitro model

Procedures: Dressing materials used were: PET (Control), fine mesh gauze coated in bismuth and petroleum jelly (BIS), nanocrystalline silver (NS), wide mesh polyester coated in polysporin ointment (WM), fine mesh cellulose acetate coated in polysporin ointment (FM), and soft silicone mesh (SIL). The dressing material was applied to gelatin and incubated for 24h. Adherence was tested using an Instron 5965 force-measurement device. Testing was repeated with various adherence reducing agents: water, surfactant, and mineral oil. Results: Adherence from least to greatest was: SIL, NS, BIS, WM, FM, PET. Water reduced adherence in all dressings; the effect increasing with exposure time. Surfactant reduced adherence of NS. Mineral oil effectively decreased adherence of BIS, and WM. Conclusion: This model allows for reproducible measurement of dressing adherence. Different interventions affect various dressings. No single intervention optimally decreases adherence for all dressings. © 2017 Elsevier Ltd and ISBI. All rights reserved.

* Corresponding author at: Department of Surgery, University of Manitoba, GF334 - Health Science Centre, 820 Sherbrook St., Winnipeg, MB R3A 1R9, Canada. Fax: +1 204-787-4063. E-mail address: [email protected] (S. Logsetty). http://dx.doi.org/10.1016/j.burns.2017.01.012 0305-4179/© 2017 Elsevier Ltd and ISBI. All rights reserved.

Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Introduction

Optimal care of burn injury remains a complex practice that in addition to surgical intervention utilises frequent dressing changes in an attempt to prevent infection and promote healing. Ideal burn dressing characteristics include absorbency, antimicrobial activity, and non-adherence [1]. While absorbency and antimicrobial activity are well studied [2,3], research on dressing adherence is lacking [4–6]. Removal of adherent dressings during dressing changes is directly associated with pain often involving the use of narcotic analgesics and even conscious sedation [7]. Furthermore, if a dressing is adherent, removal may damage the regenerating epithelium and negatively impact wound healing [8]. The effects of dressing change related pain extend beyond the physical, and have been associated with development of posttraumatic stress disorder and depression after burn injury [9,10]. In a recent survey, Selig et al. found that adherence was viewed as one of the most important dressing characteristics desired by burn care providers [11]. While absorbency and antimicrobial activity are measurable in the laboratory, adherence has posed a challenge [1]. Enterline and Salisbury described in 1980 a device for evaluating adherence of burn dressings by measuring pulling force. However this device was never evaluated in clinical use [1]. Since then, the most commonly reported method of evaluating adherence is performance of in vitro cellular adherence testing [6,12] which utilizes a solution with hydrophobic cells that does not reflect the complex environment of a wound with hydrophilic proteins. Alternative strategies have measured the force of skin graft adherence [13,14]. However, the process of skin graft adherence is different from that of dressing adherence as a complex burn wound involves other factors such as proteinaceous exudate. In addition, there is minimal evidence in the literature for what constitutes an acceptable level of adherence. The environment of and open wound or burn injury is multifaceted with not only protein but also cells and bacteria. Although an in vivo model would be ideal, these models are both difficult to run and expensive. Before embarking on a randomized controlled trial on either humans or animals, it is needed to screen the interventions using a low cost in vitro model with reasonable fidelity. Previously, we described an in vitro gelatin based model of adherence that was found to be responsive to humidity, temperature, and time [15,16]. Based on this model, we have measured adherence in vitro of commonly used burn dressings, and the effects of various interventions on dressing adherence. Herein we quantify adherence of commonly used dressings in burn care, as well as the effect of various interventions on decreasing dressing adherence.

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was placed on top of a strip of dressing slightly larger (amm) than the outside of the mold. Dressings tested included: polyethylene terephthalate (PET), the base material for many dressings; fine mesh gauze coated in Bismuth and petroleum jelly (BIS); nanocrystalline silver (NS); wide mesh polyester coated in petroleum jelly (WM); fine mesh cellulose acetate coated in petroleum jelly (FM); and soft silicone mesh (SIL). A standard amount (0.150.05g) of double antibiotic ointment (polymyxin and bacitracin) was added to each individual strip of those dressings lacking native anti-microbial agents (WM, FM, and SIL). This was done to reflect the routine practice at our center. 40% w/v gelatin was poured into the frame and allowed to set. After setting, the entire complex was placed in an incubator at what has been described as the optimal wound healing environment (32  C and 75% relative humidity) [17]. (Fig. 1) Our previous study has shown our model to be sensitive to humidity changes, however this specific humidity was chosen to best emulate a moist wound environment [15]. After 24h the samples were removed from the incubator and the respective molds and immediately analyzed. (Fig. 2) The time the samples spent outside the incubator was minimized as much as possible. The dressing was then peeled off the gelatin using an Instron 5965 (Instron, Norwood, MA) force-measurement device with a 180 peeling force test at a constant rate of 100mm/min. The Instron 5965 is a universal mechanical testing apparatus, that is not specifically designed for one end use. It offers very high accuracy and precision, load measurement accuracy to +/ 0.5% of reading down to 1/1000 of load cell capacity. It is the gold standard for mechanical testing including tensile strength and adherence testing. Adherence is a function of both pulling force and velocity; the Instron 5965 provides both of these at a constant rate. Testing was repeated a minimum of five times and 3 most consistent trials were used for analyses. Measurements obtained from the Instron machine were plotted as a function of adherence (N) against distance of peel (mm), with the x-axis ranging from 0 to 100mm. (Fig. 3) For the analysis, the range between 20 and 80mm was measured as there was increased variability near the beginning and the end of peeling test. An Excel (Microsoft Excel for Mac 2011) algorithm was used to automatically identify the five highest

Materials and methods

Using previously published standardized protocols, gelatin models were prepared [15]. A rectangular polytetrafluoroethylene (PTFE) frame with inner dimensions 16603mm

Fig. 1 – Gelatin is poured into a PTFE frame which is placed on top of the dressing strip to be tested.

Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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tray slightly larger than the gelatin sample. Then the sample was placed dressing side down into the plastic tray, with equal pressure being applied for a defined time. Following removal from the tray, the dressing was manually peeled 3–5mm from the edge of the gelatin to facilitate fixation into the Instron device. This process was performed by one individual for consistency, and required a time of approximately 30s from removal from the tray to beginning of measurement. The effect of increased exposure time (10, 30, 60 or 300s) to water on adherence was first tested on PET to define optimal testing parameters. We next tested the effect of varying surfactant concentration (0, 25, 50, 75, and 100%) on adherence on PET to standardize the concentration for use on all samples. Subsequently, the effect of all interventions on adherence was measured for all dressings. Interventions utilized were water (hydrophilic), and mineral oil (hydrophobic), and surfactant which has been historically used at our center due to its perceived effectiveness in decreasing adherence.

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Statistical analysis

Testing data are reported as means with standard deviations. Error bars as reported within charts denote the standard error of the mean. Comparisons were done with Chi square and Student’s t-test.

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Fig. 2 – Gelatin-dressing complex is removed after 24h of incubation and immediately undergoes peeling force testing. (a) Dressing being removed from the gelatin by the Instron.

peaks from within this range, from which a mean value was calculated. (Fig. 4) The highest peaks were chosen rather than an average of all the data points as clinically patients do not feel pain as an average, but rather at specific points during the peeling process. After a 24h incubation, a sample was individually removed from the incubator and tested. All samples were first tested dry, and then were tested following exposure to an intervention. 0.5mL of the desired agent was placed in recessed plastic

Results

Adherence of dry dressings from least to greatest was: SIL, NS, BIS, WM, FM, PET (Fig. 5). There was no adherence of the gelatin mold to the SIL dressing, therefore peeling force was zero (Fig. 6) and it was not possible to test and interventions. Exposure of PET to water was found to decrease adherence for all exposure times (Fig. 7), however longer exposure resulted in dissolution of the gelatin and flawed results. An exposure time of 10s was used for all dressings. The effect of varying concentrations of surfactant (25%, 50%, 75%, and 100%) at an exposure time of 10s was tested on the PET dressing, and there was found to be no difference between the different concentrations tested. (Fig. 8) Therefore, a concentration of 50% surfactant was used for measurement with the other dressings. Measurement of the various interventions on dressing adherence are presented in Fig. 9. Water was found to decrease adherence for all dressings, although this effect was minimal for NS. Surfactant decreased peeling force of all dressings apart from BIS, and was found to be the most effective intervention for NS. Mineral oil was not effective for FM and NS, mildly effective for PET, and effective for WM and BIS.

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Discussion

Despite advances in the field of burn care, dressing changes have remained a fundamental component in the treatment of burns. Apart from the impact of the initial burn injury, the effect of dressing changes also has the potential to cause significant emotional trauma to burn patients that may persist for years afterwards [9,10]. Particularly in the treatment of

Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Fig. 3 – Output of results from the Instron force measuring device for testing of a single sample, showing peeling force (N) against time (s).

burns, it is imperative to consider these other psychosocial consequences in addition to the physical nature of the burn itself. For many years at our center, it has been the standard of practice to apply water to decrease adherence of FM, WM, NS,

and BIS. It is believed that applying water to dressings to decrease adherence also decreases patients’ pain. We also use surfactant (Cida-Stat:Endure 420 Huntington Brand DIN 02240416) to decrease adherence of NS. Our preference is to use FM coated with polymyxin ointment for the majority of our

Fig. 4 – Within the output results the range from 20 to 80s was chosen to eliminate variability seen at the beginning and end phases of sample testing. Within this range the five highest peaks were identified using an automated algorithm within Excel. Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Fig. 5 – Comparison of adherence of dry dressings based on peeling force (N), arranged from highest on the left to lowest on the right.

burn patients. For patients with extensive burns, particularly those in the intensive care unit, we tend to use NS for its added benefit of decreasing dressing change frequency. At our centre, we use BIS exclusively on donor sites. However, we have not systematically measured changes in adherence due to these interventions and there is limited information available in the literature to this effect. Bell and Hart performed an in vivo assessment of dressing adherence using Silvercel and Aquacel Ag on donor sites created using a Zimmer dermatome [18]. Donor site dressings were soaked using an undefined amount of saline and removed after 5min. The force required to remove the

dressings was assessed using a five-point semi-quantative scale. In a separate study, Gourlay et al. describe an in vivo rat model where they attempted to objectify adherence using a twelve-point scale. They measured adherence at one and five days, final adherence at ten days, the degree of granulating tissue, the degree of inflammation, and vascularity [19]. Although the authors attempted to create an objective scale for dressing adherence, it was based on subjective variables. We attempt to fill this gap in the literature by measuring dressing adherence as a quantifiable force using a

Fig. 6 – Photo depicting no adherence of the gelatin to the SIL dressing, indicating a peeling force of zero. Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Fig. 7 – The effect of differing times of water exposure on the PET samples is compared against the peeling force of a dry PET sample. Water exposure times of 10, 30, and 60s are presented.

Fig. 8 – The effect of differing concentrations of surfactant on the PET samples is compared against the peeling force of a dry PET sample. Surfactant concentrations of 100%, 75%, 50%, and 25% are presented. Surfactant was mixed with water to dilute to the appropriate concentration. Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Fig. 9 – The effect of the using interventions on dressing adherence is presented. Adherence of dry dressings is compared to adherence following 10s exposures to: water, 50% surfactant, and mineral oil. No testing was performed on the SIL dressing as it showed no adherence to the gelatin.

standardized in vitro model. Our objectives were to identify the adherence of various dressings, and measure the effect that various interventions have on dressing adherence in order to determine which intervention to apply in clinical practice to decrease the pain our patients experience with dressing changes. We elected to use PET as a control in our study, as it is a base material used in many commercially available dressings and does not include any confounding additives that manufacturers may add to their dressings. Dry dressing adherence from least to greatest was: SIL, NS, BIS, WM, FM, PET. Interestingly SIL had zero adherence to the gelatin model, and so no interventions could be tested. (Fig. 6) There were some interesting findings in this study. Most notable is that NS was the second least adherent dressing in this study, while clinically this is not always the case. One explanation is that in this experiment the NS was used dry. In previous experiments when the NS was wetted prior to application of the gelatin, the adherence was much higher. NS demonstrates reduced “wettability” compared to other dressings; meaning that when dry it tends to stay dry, with initial applications of fluid to the NS just running off the material. This is seen clinically, as application of the NS dry appears to result in reduced adherence to the wound as compared to application of moist NS and letting it dry out. Further we postulate that the use of 75% relative humidity in our model may have also been a factor. We also observe

that keeping the NS moist for the duration of the experiment reduces the final adherence. While 75% relative humidity was chosen for this experiment as an ideal wound healing environment, it may not accurately represent the surface of a burn wound. In the future, we plan to measure the relative humidity and temperature of various depths of burn wounds to be able to better simulate these conditions in vitro. Of note is that the surfactant improves the wettability of the NS material making it easier to remove (Fig. 10).

Fig. 10 – The NS dressing demonstrates reduced “wettability” compared to other dressings; meaning that when dry it tends to stay dry, and when wet it tends to stay wet.

Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012

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Table 1 – Summary of recommended interventions to use for specific dressing types, based on our results. Dressing material

Intervention to use

PET

Water Surfactant

WM

Water Surfactant Mineral oil

FM

Water

NS

Surfactant

BIS

Water Mineral oil

In order to standardize the exposure time of our interventions, we first examined the effect that water had on adherence of PET with increased durations of time. (Fig. 7) An exposure time of ten seconds was chosen for all exposures as the trend observed suggests this was still on the descending portion of the curve. It was felt at a longer exposure times, a plateau would be reached and it would be difficult to make comparisons between various interventions. At an exposure time of 900s, water began to dissolve the gelatin. These results were not included in our analysis as this was felt to be a physical limitation of the model rather than a representation of what would be observed clinically. Based on our findings, we compiled a summary of recommended interventions to use for specific dressing types (Table 1). In our future work, we hope to apply the results from these in vitro studies to an in vivo model of burn dressing adherence quantification using a hand-held force meter. We will measure the adherence of dressings the burns during dressing changes, as well as the pain that patients experience during these dressing changes. We will attempt to determine if there is a correlation between our in vitro and in vivo adherence measurements, and what the relationship between adherence and pain is in patients.

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Conclusions

Our standardized and validated gelatin model allows for reproducible measurement of quantifiable dressing adherence, both in their dry state and following exposure to various interventions aimed at decreasing adherence. Different interventions were found to have a different impact on various dressings, with no single intervention being optimal for decreasing adherence in all dressing types. Although our findings largely coincide with our clinical observations, our model is not entirely representative. Future directions will focus on refining our model to more accurately simulate the surface of burn wounds, and also to apply these results in vivo to determine the correlation between adherence and pain experienced by patients.

Conflict of interest There are no financial conflicts of interest relevant to this study for any of the authors.

Funding sources

(1) Manitoba Health Research Council (MHRC) Operating grant. (2) Collaborative Health Research Projects (CHRP) Operating grant (Grant no.: CHRP 413713-2012). (3) Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (Grant no.: RGPIN/3720482009). (4) Manitoba Firefighters Burn Fund.

Additional information (1) Each of the authors has contributed to, read and approved this manuscript. (2) This manuscript has not been previously published, nor is it under consideration elsewhere. REFERENCES

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Please cite this article in press as: M. Brichacek, et al., In vitro measurements of burn dressing adherence and the effect of interventions on reducing adherence, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.01.012